The results of our systematic review provide limited evidence for the effectiveness of CAM therapy in relieving symptoms of CFS. However, we are not able to draw firm conclusions concerning CAM therapy for CFS due to the limited number of RCTs for each therapy, the small sample size of each study and the high risk of bias in these trials. Further rigorous RCTs that focus on promising CAM therapies are warranted

1. RESEARCH ARTICLE Open Access
Complementary and alternative medicine
for patients with chronic fatigue syndrome:
A systematic review
Terje Alraek1*†
, Myeong Soo Lee2†
, Tae-Young Choi2
, Huijuan Cao3
and Jianping Liu1,3
Abstract
Background: Throughout the world, patients with chronic diseases/illnesses use complementary and alternative
medicines (CAM). The use of CAM is also substantial among patients with diseases/illnesses of unknown aetiology.
Chronic fatigue syndrome (CFS), also termed myalgic encephalomyelitis (ME), is no exception. Hence, a systematic
review of randomised controlled trials of CAM treatments in patients with CFS/ME was undertaken to summarise
the existing evidence from RCTs of CAM treatments in this patient population.
Methods: Seventeen data sources were searched up to 13th August 2011. All randomised controlled trials (RCTs)
of any type of CAM therapy used for treating CFS were included, with the exception of acupuncture and complex
herbal medicines; studies were included regardless of blinding. Controlled clinical trials, uncontrolled observational
studies, and case studies were excluded.
Results: A total of 26 RCTs, which included 3,273 participants, met our inclusion criteria. The CAM therapy from
the RCTs included the following: mind-body medicine, distant healing, massage, tuina and tai chi, homeopathy,
ginseng, and dietary supplementation. Studies of qigong, massage and tuina were demonstrated to have positive
effects, whereas distant healing failed to do so. Compared with placebo, homeopathy also had insufficient
evidence of symptom improvement in CFS. Seventeen studies tested supplements for CFS. Most of the
supplements failed to show beneficial effects for CFS, with the exception of NADH and magnesium.
Conclusions: The results of our systematic review provide limited evidence for the effectiveness of CAM therapy in
relieving symptoms of CFS. However, we are not able to draw firm conclusions concerning CAM therapy for CFS
due to the limited number of RCTs for each therapy, the small sample size of each study and the high risk of bias
in these trials. Further rigorous RCTs that focus on promising CAM therapies are warranted.
Background
Throughout the world, patients with chronic diseases tend
to be high utilisers of health care resources and/or the
health care system. Such patients are also frequent users
of Complementary and Alternative Medicine (CAM) ser-
vices, which are present either within or outside the
National Health Service. The reasons for using CAM are
diverse; however, hope, engagement in one’s own health
and positive expectations of treatment efficacy are nearly
always present. Patients with chronic fatigue syndrome
(CFS) are no exception. CFS is a challenging illness for
patients, as well as those close to them, health care provi-
ders and society in general. Western medicine usually has
potent treatments readily available for diseases with a sin-
gle cause and a well-described pathophysiology. However,
as of yet, no single cause of CFS has been discovered,
although potential factors, which are still questionable,
have been identified [1-3]. Several treatments for this
condition have been explored; however, none has shown
persistent or consistently significant outcomes in this
patient population [4-6]. Although several CAM treat-
ments for CFS patients were described in a previous
review, the review only included literature up to April
2007 [7]. Furthermore, a new quality assessment tool (the
Cochrane risk of bias tool) has since been proposed to
* Correspondence: terje.alrak@uit.no
† Contributed equally
1
National Research Center for Complementary and Alternative Medicine,
University of Tromsø, Norway
Full list of author information is available at the end of the article
Alraek et al. BMC Complementary and Alternative Medicine 2011, 11:87
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© 2011 Alraek et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.

2. enhance the validity of systematic reviews [8]. Therefore,
the aim of our review was to systematically summarise
and critically evaluate the data from RCTs of CAM treat-
ment for patients with CFS.
Methods
Data sources
We searched the following electronic databases up
to 13th
August 2011: Medline, PsycInfo, Alternative
Medicine (AMED), the Cumulative Index to Nursing &
Allied Health Literature (CINAHL), EMBASE, and the
Cochrane Library 2011 (Issue 5). We also searched the
Chinese databases (China Network Knowledge Infra-
structure (CNKI; 1979-2010), the Chinese Scientific Jour-
nal Database VIP (1989-2010), the Wan Fang Database
(1985-2010), and the Chinese Biomedicine (CBM) data-
base (1978-2010); the Korean medical databases (includ-
ing Korean Studies Information, DBPIA, Korea Institute
of Science and Technology Information, Research Infor-
mation Service System, KoreaMed, and National Assem-
bly Library); and Japanese databases (Japan Science and
Technology Information Aggregator, Electronic). The
search strategy is listed in Additional file 1. In addition,
we manually searched our own files, Focus on Alternative
and Complementary Therapies and Forschende Komple-
mentärmedizin. The references in all located articles
were also searched.
Selection Criteria
All randomised controlled trials (RCTs) of any type of
CAM therapy, with the exception of acupuncture and
complex Chinese herbal medicines, for the treatment of
CFS were included, regardless of blinding or the pub-
lished language. Cochrane reviews of trials testing acu-
puncture type therapies [9] are ongoing, and as a result,
this topic was excluded. We included RCTs that tested a
single herb for CFS. RCTs testing complex herbal medi-
cines for CFS were excluded, as it is not possible to iso-
late the effects of single herbs. Trials were included if
they used CAM as either the sole treatment or as an
adjunct to other treatments, which occurred in cases
where the control group also received the same concomi-
tant treatments as the CAM group. Studies comparing
two different forms of CAM and those in which no clini-
cal data were reported were also excluded. Cognitive
behavioural interventions were not considered to be a
part of CAM and were therefore excluded. If cognitive
behavioural intervention was used as a control, the trial
was included. Trials that employed CAM as the sole
treatment or as an adjunct to other treatments were
included. Dissertations and abstracts were included if
they contained sufficient detail for critical evaluation.
Hard copies of all articles were obtained.
Data Extraction, Quality, and Risk of Bias Assessment
All articles were read, and data were extracted from the
articles based on predefined selection criteria by two
independent reviewers (MSL and TYC). To evaluate the
methodological quality of the RCTs, the risk of bias was
determined using the Cochrane classification for eight
criteria: random sequence generation, allocation conceal-
ment, patient blinding, assessor blinding, reporting of
dropout or withdrawal, intention-to-treat analysis, selec-
tive outcome reporting and other potential biases [8].
Results
Study description
We screened 647 relevant articles, and 592 were
excluded, leaving us with 55 full-text eligible articles. Of
these, 29 more were excluded. The remaining 26 RCTs
met our inclusion criteria (Figure 1).
Key data from these studies are summarised in Tables 1
and 2 [10-35]. The RCTs included in the table employed
the following treatments: mind-body medicine (4) [10-13],
massage (2) [14,15], tuina and tai chi (1) [16], homeopathy
(2) [17,18], ginseng (1) [19], nicotinamide adenine dinu-
cleotide (NADH) (2) [20,21], and dietary supplements (14)
[22-35]. A placebo procedure was employed in 16 trials
[17-20,22-27,29-34]. Twenty of the included trials adopted
a two-arm parallel group design [10-12,14,15,17-27,
29,30,33,35], three adopted a three-arm parallel group
design [16,28,34], and one used a four-arm parallel group
design [13], while two trials employed a cross-over design
[31,32]. Nine trials adopted the CDC criteria for the diag-
nosis of CFS [11,20,22,24,25,27,28,31,32], five studies
diagnosed CFS according to the criteria published by
Fukuda [10,15,16,19,21], five used the Oxford criteria
[12,17,18,30,35], two combined with Fukuda and Oxford
criteria [13,23], and one used a different classification
system [33].
Risk of bias
The risk of bias in the studies was variable. Eleven RCTs
had an adequate method for random sequence generation
[10,11,13,15,17,19,24,25,28,29,33], whereas the remaining
15 RCTs did not [12,14,16,18,20-23,26,27,30-32,34,35].
Allocation concealments were adequately performed in 13
RCTs [10,11,13,17,19,24,25,29-33]. Patient and assessor
blinding was reported in 16 of the RCTs [17-20,22-27,
29-34], whereas two RCTs employed assessor blinding
only [10,11]. Reasons for dropouts and withdrawals
were fully described in 17 trials [10,11,13,17,19,22-26,
28-30,32-35]. With respect to the intention-to-treat (ITT)
analysis, 11 RCTs did not report the basis of the analysis
[11,12,14-16,28,30-32,34,35], and 9 were analysed on a
per-protocol basis [10,13,18,20,21,23,25-27]. The remain-
ing 6 studies employed the ITT method [17,19,22,
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3. 24,29,33]. Eleven RCTs had a low risk of bias in selective
outcome reporting [11,13,14,17-19,21,23,25,29,33], and the
others had a high risk of such bias.
Mind-body and energy medicine
Two RCTs compared qigong plus meditation with no
treatment [10,11]. Both studies reported beneficial
effects of qigong with meditation on fatigue. One RCT
tested Mindfulness Based Stress Reduction (MBSR) as
compared with a wait-list control and found significant
effects of the treatment on anxiety [12]. The other RCT
compared distant healing with a four-armed partial
blinding, placebo-controlled design and did not show a
significant effect on mental or physical components of
quality of life [13].
Massage
Two RCTs tested massage compared with Sham TENS
or another type of massage [14,15]. One RCT demon-
strated the beneficial effects of massage on several symp-
toms of CFS, including depression, fatigue, pain and
insomnia [14]. The other RCT compared a special type of
massage (Intelligent-turtle) with general massage and
reported some effect of this type of massage on physical
symptoms [15].
Tuina and tai chi
One RCT tested tuina and tai chi as compared to fluoxe-
tine [16]. The tuina group had more symptom reduction
than the fluoxetine group fluoxetine, but there were no
significant differences between tuina and tai chi or tai chi
647 records screened
55 full-text articles
assessed for eligibility
26 studies included in
qualitative synthesis
637 records identified through
database searching
10 additional records identified
through hand-searching
592 records excluded on
the basis of title and
abstract
29 full-text articles
excluded:
CCT (n=2)
NCT (n=5)
UOS (n=1)
Not related to CAM
(n=17)
Review (n=3)
Not related to CFS
(n=1)
Figure 1 Flow diagram of literature search. CCT: controlled clinical trial; NCT: not clinical trial; UOS: uncontrolled observational study; CAM:
complementary and alternative medicine; CFS: chronic fatigue syndrome
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4. Table 1 Summary of randomised clinical studies of complementary and alternative medicine for patients with chronic fatigue syndrome
First author
(year)
Sample size Diagnosis Intervention group (Regime) Control group (Regime) Main outcomes Intergroup
differences
Adverse events
Gender (M/F)
Mean age
(range)
Clollinge
(1998) [10]
70 Fukuda (A) Qigong (2 hr weekly for 9 weeks, n
= 37) plus mindfulness meditation and
group discussion
(B) No treatment (n = 33) SF-36 Heath
transition score
No
between
group
analysis
n.r.
(10/50)
27-61
Dybwad
(2007) [11]
31 (4/27) CDC (A) Qigong (2 hr weekly for 12 weeks),
plus meditation, n = 15)
(B) No treatment (n = 16) 1) Work capacity
(VO2max)
1) P = 0.01 n.r.
17-62 2) Fatigue
severity
2) P < 0.05
3) SF36 3) NS
Surawy
(2005) [12]
18 Oxford (A) MBSR
(once weekly for 8 weeks, n = 8)
(B) Wait-list
(once weekly for 8 weeks, n = 9)
1) HADS Anxiety 1) P = 0.00 n.r.
10/8 2) HADS
Depression
2) NS
18~65 3) Chalder
Fatigue Scale
3) NS
(n.r) 4) SF36 Physical
Functioning
4) NS
Walach
(2008) [13]
409 Fukuda or
Oxford
(A) Distant healing (blinded, n = 105) (C) No distant healing (blinded,
n = 95)
SF-36 NS for both
the mental
and
physical
component
n.r.
(B) Distant healing
(not blinded, n = 102)
(D) No distant healing
(not blinded, n = 109)
Field (1997)
[14]
20 Not
stated
(A) Massage therapy (twice weekly for 5
weeks, n = 10)
(B) Sham TENS (twice weekly for
5 weeks, n = 10)
1) CESD 1) P < 0.005 n.r.
4/16 2) Fatigue 2) P < 0.05
n.r. 3) Pain 3) P < 0.005
-47 4) Sleep 4) P < 0.05
Wang (2009)
[15]
182 Fukuda (A) Intelligent-turtle massage (5 times
weekly, 10 times as a course, for 2
courses with a one-week interval in
between, n = 91)
(B) Massage(45 min, 5 times a
week, 10 times as a course,
n = 91)
Physical
Symptoms
P < 0.05 n.r.
141/40
21-62
(n.r)
Liu (2010)
[16]
90 (44/46) Fukuda (A) Tuina
(once 2 days for 15 times, n = 30)
(C) Fluoxetine (20 mg/d, 1
month, n = 30)
Total effective
rate
A vs. B, NS;
A vs. C, P <
0.05; B vs. C,
NS
(C); 17 insomnia dizziness vexation nausea,
hypodynamia
26.4~46.2 (B) Tai chi (n.r., 1 month, n = 30)
(n.r.)
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5. Table 1 Summary of randomised clinical studies of complementary and alternative medicine for patients with chronic fatigue syndrome (Continued)
Weatherley-
Jones (2004)
[17]
103/92 Oxford (A) Homeopathy (6 months, n = 47) (B) Placebo
(6 months, n = 45)
1) MFI 1) NS
except
general
fatigue, P =
0.04
n.r.
n.r. 2) FIS 2) NS
Over 18 years 3) FLP 3) P = 0.04
(n.r)
Awdry
(1996) [18]
64/61 Oxford (A) Homeopathy (1 year, n = 30) (B) Placebo
(n = 31)
1) Daily graphs 1-2) No
between
n.r.
18/43 2) Symptoms
score
group
analysis
<65
(n.r.)
Hartz Hartz
(2004) [19]
96/76 Fukuda (A) Ginseng (Siberian, 2 months, n = 40 (B) Placebo
(16 weeks, 2 month, n = 36)
RVI NS n.r.
n.r.
21~65
(n.r)
Forsyth
(1999) [20]
26 CDC (A) NADH (10 mg, once daily for 4
weeks, n = 26, cross over design)
(B) Placebo(n = 26) Symptom score P < 0.05 Overly stimulated, mild loss of
appetite, heartburn, increased
incidence of gas and an odd taste
and dryness (1)
(9/17)
26-57
-39.6
Santaella
(2004) [21]
31 Fukuda (A) NADH or nutritional (B) Psychological therapy (24
months, n = 11)
Symptom score
(month 3)
P < 0.001 n.r.
n.r. supplements
(5-10 mg, 24 months, n = 20)
22~54
(n.r)
Brouwers
(2002) [22]
53 CDC (A) General nutritional supplement
(twice a day for 10 weeks, n = 27)
(B) Placebo(n = 26) 1) Fatigue
severity
1)-3) NS n.r.
(16/37) 2) Functional
impairment
n.r. 3) Physical
activity levels
-39.3
De Becker
(2001) [23]
90 Fukuda or
Holmes
(A) Acclydine (250 mg, 4 times daily for
1st
4 weeks and 250 mg, twice daily for
2nd
4 weeks, n = 45)
(B) Placebo (n = 45) CGI No
between
group
analysis
n.r.
n.r.
n.r.
(n.r.)
The (2007)
[24]
57 CDC (A) Food supplement (Acclydine 1000
mg to 250 mg for 14 weeks, n = 30)
(B) Placebo (n = 27) 1) Fatigue
severity
1)-4) NS Mild nausea (1), exacerbation of CFS
symptoms (1) and irritable bowel symptoms
(1)
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6. Table 1 Summary of randomised clinical studies of complementary and alternative medicine for patients with chronic fatigue syndrome (Continued)
(20/37) 2) Function
impairment
n.r. 3) Activity level
(n.r.) 4) Daily fatigue
level
McDertmott
(2006) [25]
71 CDC (A) Food supplement (Biobran 2 mg
three times per day for 8 weeks, n = 37)
(B) Placebo(n = 34) 1) Fatigue scale 1) NS
(20/51) 2) QOL 2) NS
n.r. (WHOQOL_BREF)
(n.r.)
Stewart
(1987) [26]
12 Not
stated
(A) Supplements (subjects given
supplements for 3 weeks, after first 3
weeks cross-over treatment arms for
further 3 weeks, 2 multi-digestive
enzymes, crossover design n = 12)
(B) Placebo(n = 12) 1) Fatigue 1)-2) No
between
group
analysis
n.r.
n.r. 2) Bowel
movements
n.r.
(n.r.)
Rothschild
(2002) [27]
70/68 CDC (A) Supplement (mushrooms plus aloe
vera and cat’s claw, processed and
fermented, 3 caplets taken 3 times daily
before meals, n = 33)
(B) Placebo (n = 35) Symptoms No
between
n.r.
20/50 group
analysis
n.r.
(n.r.)
Vermeulen
(2004) [28]
90 CDC (A) Acetyl-L-carnitine (2 g daily for 24
weeks, n = 30)
(B) Propionyl-L-carnitine (n = 30) 1) Fatigue scale No
between
group
analysis
n.r.
(21/69) (C) A plus B (n = 30) 2) Pain
n.r. 3) Attention/
concentration
(n.r.)
Behan
(1990) [29]
63 Not
stated
(A) Fatty acids((Efamol Marine, 8
capsules per day, n = 39)
(B) Placebo (n = 24) 1) Symptom
measure
1) P < 0.001 n.r.
27/36 2) General
health
2) P <
0.0001
21-63 3) n.r.
-40
Warren
(1999) [30]
50 Oxford (A) Essential fatty acids (Efamol Marine
1000 mg 4 times a day for 3 months, n
= 25)
(B) Placebo (n = 25) 1) Physical
symptom
1) NS n.r.
(21/29) 2) Depression
(Beck
Depression
Inventory)
2) NS
18-59
-35.7
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7. Table 1 Summary of randomised clinical studies of complementary and alternative medicine for patients with chronic fatigue syndrome (Continued)
Kaslow
(1989) [31]
14 CDC (A) Liver extract-folic acid-
cyanocobalamin (intramuscular injection
2 ml for 1-week, n = 14, crossover
design)
(B)Placebo (n = 14) Functional status
questionnaire
NS None
(3/11)
30-48
(n.r.)
Ockerman
(2000) [32]
22 CDC (A)Antioxidant treatment (pollen and
pistil 7 tablets per day for 3 months,
n = 22, cross-over design)
(B) Placebo (3 month, n = 22) 1) Total well-
being
1) No
between
group
analysis
n.r.
(3/19) 2) Clinical
symptoms
2) No
between
group
analysis
27-70
-50
Cox (1991)
[33]
34/31 other (A) Vitamin and minerals
(Magnesium, 6 weeks, n = 14)
(B) Placebo (6 weeks, n = 17) Mean
Nottingham
P = 0.001 n.r.
11/23 health profile
score
18~56
(n.r.)
Tiev (1999) 326 Not
stated
(A) Sulbutiamine (400 mg (C) Placebo (n = 109) 1) MFI 1) Sleep
disturbance
(A):9,(B):6,(C):12 diarrhoea, cystitis, bronchitis,
arthritic pain, back pain, asthma, abdominal
pain, insomnia, constipation, gastroenteritis,
diffuse pain, sinusitis, headache, renal coli,
vertigo, pharyngitis, tracheitis.
daily, n = 106) 2) Clinical global
impression
(p = 0.03)
(B) Sulbutiamine (600 mg 3) Baecke’s
measure of
activity
Pain (p =
0.044)
daily, n = 111) 4) Illness severity 2) NS
3) NS
Willams
(2002) [35]
30 Oxford (A) Melatonin (5 mg in the (B) phototherapy (2500 Lux for 1 1) VAS for
symptom
severity; SF-36
1) Sleep
disturbance
(p = 0.03);
Pain (p =
0.044)
n.r.
13/17 evening, 12 week, n = 30) hour in the morning, 12 weeks,
n = 30)
2) Mental
fatigue
2) NS
n.r. 3) HADS 3) NS
-44.5
CDC: Centers for Disease Control and Prevention; CESD: Center for Epidemiological Studies Depression Scale; CFS: Chronic Fatigue Syndrome; CGI: Clinician’s Global Impression Scale; FIS: Fatigue Impact Scale; FLP:
Functional Limitations Profile; HADS: Hospital Anxiety and Depression Scale; MBSR: Mindfulness-Based Stress Reduction; MFI: Multidimensional Fatigue Inventory; n.r.: not reported; NS: Not significant; RVI: Rand
Vitality Index; NADH: Nicotinamide adenine dinucleotide; QoL: Quality of life; SF-36: Short Form 36; VAS: Visual Analogue Scale; WHOQOL-BREF: WHO Quality of Life-BREF.
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8. Table 2 Risk of bias of included RCTs*
Study Random sequence
generation
Allocation
concealment
Patient
blinding
Assessor
blinding
Reporting drop-out or
withdrawal†
Intention-to-treat
analysis†
Selective outcome
reporting
Other potential
bias
Clollinge (1998) [10] Low Low High Low Low High High Unclear
Dybwad (2007) [11] Low Low High Low Low Unclear Low Low
Surawy (2005) [12] Unclear Unclear High Unclear High Unclear Unclear Unclear
Walach (2008) [13] Low Low Low Low Low High Low Low
Field (1997) [14] Low Unclear High High Unclear Unclear Unclear High
Wang (2009) [15] Unclear Unclear Low Low High Unclear Low Unclear
Liu (2010) [16] Unclear Unclear High Unclear Unclear Unclear Unclear Unclear
Weatherley-Jones
(2004) [17]
Low Low Low Low Low Low Low Low
Awdry (1996) [18] Unclear Unclear Low Low High High Low Unclear
Hartz (2004) [19] Low Low Low Low Low Low Low Low
Forsyth (1999) [20] Unclear Unclear Low Unclear Unclear High Unclear Unclear
Santaella (2004) [21] Unclear Unclear High High High High Low Unclear
Brouwers (2002) [22] Unclear High Low Low Low Low Unclear Low
De Becker (2001) [23] Unclear Low Low Unclear Unclear Unclear Unclear Low
The (2007) [24] Low Low Low Low Low Low Unclear Low
McDertmott (2006)
[25]
Low Low Low Low Low High Low Low
Stewart (1987) [26] Unclear Unclear High High Low High High Unclear
Rothschild (2002) [27] Unclear Unclear Low Low High High Unclear Unclear
Vermeulen (2004)
[28]
Low Low Low Low Low Low Low Low
Behan (1990) [29] Low Low High High Low Unclear High Unclear
Warren (1999) [30] Low Low Low Low Low Low Low Unclear
Kaslow (1989) [31] Unclear Low Low Low Low Unclear Unclear Low
Ockerman (2000) [32] Unclear Low Low Low Low Unclear Unclear Low
Cox (1991) [33] Unclear Unclear Low Low Unclear High Low Unclear
Tiev (1999) [34] Unclear Unclear Unclear Unclear Low Unclear Unclear Unclear
Willams (2002) [35] Unclear Unclear Unclear Unclear Low Unclear Unclear Unclear
*, Domains of quality assessment based on Cochrane tools for assessing risk of bias.
†
, Two domains referring to ‘incomplete outcome data’ in the Cochrane tools for assessing risk of bias.
‡
, This study had a baseline imbalance in the subjective outcome values.
Abbreviations; Low (low risk of bias);/High (high risk of bias); Unclear (uncertain risk of bias).
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9. and fluoxetine after 1 month of treatment. The effective
rate was decided by the practitioner and was based on
symptom improvement, which was not described in
detail.
Homeopathy
Two RCTs compared homeopathy with placebo [17,18].
One RCT showed that homeopathy improved fatigue
and function [17]. The other RCT reported the benefi-
cial effects of homeopathy on symptom improvement
[18].
Ginseng
One RCT tested Siberian ginseng and failed to show the
effectiveness of ginseng on the Rand Vitality Index [19].
Supplements
Two RCTs compared NADH with placebo or psychologi-
cal therapy [20,21]. One RCT showed statistically signifi-
cant effects of NADH (10 mg) on symptom scores when
compared with placebo after 1 month of treatment [20].
The other RCT also reported the positive effects of
NADH (from 5 to 10 mg) when compared with psycholo-
gical therapy (not reported in details) after 3 months [21].
Six RCTs compared several types of general food supple-
ments with a placebo control [22-27]. Five of these RCTs
failed to show significant effects of dietary supplements on
symptoms of CFS when compared with placebo. One RCT
compared acclydine with placebo and showed the benefi-
cial effects of acclydine on clinical improvement at weeks
4 and 8 [23].
One RCT tested Acetyl-L-carnitine as compared with
Propionyl-carnitine and combined both therapies [28].
The results showed the beneficial effects of each therapy
on fatigue, pain and attention/concentration.
Two RCTs compared essential fatty acids (Efamol Mar-
ine-evening primrose oil) with placebo [29,30]. One RCT
showed the possible efficacy of essential fatty acids on
symptoms and general heath [29], whereas the other RCT
failed to show an impact of this therapy on physical symp-
toms and depression when compared to placebo [30].
One RCT compared liver extract-folic acid-cyanoco-
balamin with placebo and failed to show an effect for the
treatment [31]. The second RCT compared antioxidant
treatment with placebo and reported beneficial effects in
the treatment group; however, there were no reports on
intergroup differences [32]. The third RCT compared a
magnesium supplement with placebo and found beneficial
effects of magnesium on patients’ symptom profiles [33]. A
large, double-blind RCT of patients with CFS investigated
the effect of isobutyryl-thiamine disulphide. No improve-
ments were observed when compared with placebo [34].
When melatonin was compared in an RCT with photother-
apy, neither intervention generated beneficial effects [34].
Adverse events
Five of the 26 included studies reported no adverse
events or a slight occurrence of them [16,20,24,31,34],
whereas the remaining 20 studies lacked descriptions
regarding the occurrence of adverse events.
Discussion
Our analysis shows that a range of CAM studies have been
conducted to determine which therapies might ameliorate
CFS symptoms. There is insufficient evidence to conclu-
sively determine efficacy. Studies of qigong, massage and
tuina have demonstrated positive effects; however, the nat-
ure of the control group and the quality of the studies pre-
vent us from concluding that those CAM therapies are
effective for CFS. Compared with placebo, homeopathy
also had insufficient evidence of symptom improvement in
CFS. Seventeen studies tested supplements for CFS. Most
of the supplements failed to show favourable effects for
CFS, with the exception of NADH and magnesium. How-
ever, the total number of RCTs and the total sample size
were too small to draw firm conclusions.
Our review aimed to update and complete the evi-
dence of CAM treatments for symptom relief in patients
with CFS. Compared to a previous review [7], we identi-
fied 3 new types of CAM and 9 new RCTs and success-
fully updated the evidence for these therapies in CFS.
The results of our review are similar to that of the pre-
vious review [7], which also expressed concern regarding
the poor methodological quality of the included primary
studies [7]. Another two published reviews concerning
traditional Chinese medicine and herbal medicines were
unable to find appropriate studies to review [36,37].
Most of the included trials had a high risk of bias in
many domains. Low quality trials are more likely to
overestimate effect size [38]. This is also true for trials
with inadequate blinding and inadequate allocation con-
cealment, as such trials are more subject to selection
bias and are likely to generate exaggerated treatment
effects [38,39]. Several trials used an inadequate method
for sequence generation. Because inadequate sequence
generation in randomisation studies also tends to yield a
larger estimate of treatment effects, this is another
source of potential bias.
One argument for using CAM for the management of
CFS might be that it causes fewer adverse effects than
drug treatment. Only five RCTs [16,20,24,31,34] assessed
the adverse effects of CAM treatment, while 21 RCTs
did not. No severe adverse effects of CAM were noted.
However, adverse effects should be assessed in future
CAM trials. This is an important factor for patients, as
CAM treatments are generally offered outside of the
official health care system.
Our review has a number of important limitations.
Although strong efforts were made to retrieve all RCTs on
the subject, we cannot be absolutely certain that we suc-
ceeded. Moreover, selective publishing and reporting are
other major causes for bias, which must be considered
Alraek et al. BMC Complementary and Alternative Medicine 2011, 11:87
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10. [40,41]. It is conceivable that several negative RCTs
remain unpublished, thus distorting the overall picture
[40,42]. Further limitations include the paucity and often
suboptimal methodological quality of the primary data.
Together, these factors limit the conclusiveness of this sys-
tematic review considerably.
Conclusions
The results of our systematic review provide limited evi-
dence for the effectiveness of CAM in treating patients
with CFS. However, the total number of RCTs included
in the analysis, the total sample size and their risk of bias
were quite high in several domains; thus, drawing firm
conclusions concerning the effectiveness of CAM thera-
pies remains difficult. Further rigorous RCTs that can
overcome the many limitations of the current literature
are warranted.
Additional material
Additional file 1: Search Strategy
Acknowledgements
This study was supported with a grant from the Norwegian Directorate of
Health
Author details
1
National Research Center for Complementary and Alternative Medicine,
University of Tromsø, Norway. 2
Brain Disease Research Center, Korea Institute
of Oriental Medicine, Daejeon, South Korea. 3
Center for Evidence-Based
Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
Authors’ contributions
TA obtained funding for the study, conceived and participated in its design
and coordination and helped to draft the manuscript. MSL conceived and
participated in its design. MSL and TYC searched databases, extracted and
assessed studies. They also helped to draft the manuscript. HC participated
in the study design and helped to draft the manuscript. JL conceived the
study, and participated in its design and helped to draft the manuscript. All
authors read and approved the final manuscript.
Competing interests
The authors declare that they have no competing interests.
Received: 10 June 2011 Accepted: 7 October 2011
Published: 7 October 2011
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Cite this article as: Alraek et al.: Complementary and alternative
medicine for patients with chronic fatigue syndrome: A systematic
review. BMC Complementary and Alternative Medicine 2011 11:87.
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